Mutations in an Innate Immunity Pathway Are Associated with Poor Overall Survival Outcomes and Hypoxic Signaling in Cancer

Monica M. Olcina, Nikolas G. Balanis, Ryan K. Kim, B. Arman Aksoy, Julia Kodysh, Michael J. Thompson, Jeff Hammerbacher, Thomas G. Graeber, Amato J. Giaccia

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Complement-mediated cytotoxicity may act as a selective pressure for tumor overexpression of complement regulators. We hypothesize that the same selective pressure could lead to complement alterations at the genetic level. We find that, when analyzed as a pathway, mutations in complement genes occur at a relatively high frequency and are associated with changes in overall survival across a number of cancer types. Analysis of pathways expressed in patients with complement mutations that are associated with poor overall survival reveals crosstalk between complement and hypoxia in colorectal cancer. The importance of this crosstalk is highlighted by two key findings: hypoxic signaling is increased in tumors harboring complement mutations, and hypoxic tumor cells are resistant to complement-mediated cytotoxicity due, in part, to hypoxia-induced expression of complement regulator CD55. The range of strategies employed by tumors to dysregulate the complement system testifies to the importance of this pathway in tumor progression.

Original languageEnglish
Pages (from-to)3721-3732.e6
JournalCell Reports
Volume25
Issue number13
DOIs
StatePublished - 26 Dec 2018

Keywords

  • cancer
  • complement system
  • complement-mediated cytotoxicity
  • hypoxia
  • innate immunity
  • mutations

Fingerprint

Dive into the research topics of 'Mutations in an Innate Immunity Pathway Are Associated with Poor Overall Survival Outcomes and Hypoxic Signaling in Cancer'. Together they form a unique fingerprint.

Cite this